In order to dissect the molecular mechanisms whereby HIV-1 functionally alters or kills CD4+ T lymphocytes a series of transfected Jurkat cell lines expressing different HIV-1 proteins were established. Cells constitutively expressing functional gp120 and gp41 had no alterations in cell growth nor in their ability to support the growth of HIV-1. Cells expressing HIV-1 nef appeared normal in expressing IL-2 and in supporting HIV-1 replication. Transfection of Jurkat T cells with HIV-1 envelope in defined situations resulted in the production of truncated p75 envelope- related protein. HIV-1 infection of a variety of CD4+ cells or tumors led to increases in two tyrosine-phosphorylated proteins of 95 and 40 kilodaltons while phosphoproteins pp56 a pp59, likely I corresponding to p56 Ick and p59fyn, were unaltered. Peripheral blood CD4+ T lymphocytes infected in vitro with HIV-1 were found to give rise to CD4-/CD8- gamma/delta T lymphocytes that did not express IL-2 following stimulation. In studies on the peripheral blood mononuclear cells of patients with HIV infection an increased proportion of cells expressing the gamma/delta T cell receptor were identified. Two variable region immunoglobulin genes encoding human antibodies directed against gp4l were cloned.